Substituted tricyclic thieno compounds, their synthesis, their use, their compositions and their medicaments

Abstract

Substituted thienobenzodiazepinones of the general formula I ##STR1## [wherein R 1 denotes a hydrogen atom (--H) or an alkyl radical with 1 to 4 carbon atoms; R 2 represents a halogen atom (halo) or has one of the meanings of R 1 ; R 3 denotes a halogen atom (halo) or the group --N(R 4 )R 5 ; R 4 denotes an alkyl radical with 1 to 4 carbon atoms or an alkenyl radical with 3 to 5 carbon atoms; R 5 has one of the meanings of R 4 or represents the group --(CH 2 ) m --N(R 6 )R 7 ; or R 4 and R 5 , together with the nitrogen atom to which both are bonded, denote a morpholino group, a pyrrolidino group, a piperidino group, a hexahydroazepin-1-yl group, a piperazin-1-yl group (which is optionally substituted in the 4-position by a methyl, ethyl or benzyl group), a 2,4-dimethylpiperazin-1-yl group, or a hexahydro-1H-1,4-diazepin-1-yl group (which is substituted in the 4-position by a methyl or ethyl group); R 6 denotes an alkyl group with 1 to 4 carbon atoms; R 7 denotes an alkyl group with 1 to 4 carbon atoms; A denotes a straight-chain or branched alkylene group with 1 to 5 carbon atoms; and m denotes 2 or 3] and their acid-addition salts are new compounds. They either have a protective action on the stomach and intestine and are suitable for treating illnesses based on disorders of the stomach or intestine, or they are intermediates for preparing products having protective action. Processes for the preparation of the new pharmacologically-active compounds and of the intermediate products are presented.

What is claimed is: 
     
       1. A substituted thienobenzodiazepinone of the formula ##STR5## wherein R 1  denotes a hydrogen atom (-H) or alkyl with from 1 to 4 carbon atoms, R 2  represents halo or has one of the meanings of R 1 ,   R 3  denotes halo or -N(R 4 )R 5 ,   R 4  denotes alkyl with from 1 to 4 carbon atoms or alkenyl with from 3 to 5 carbon atoms,   R 5  denotes one of the meanings of R 4  or --(CH 2 ) m  --N(R 6 )R 7  or N(R 4 )R 5  denotes morpholino, pyrrolidino, piperidino, hexahydroazepin-1-yl, piperazin-1-yl which is optionally substituted in the 4-position by methyl, ethyl or benzyl, 2,4-dimethylpiperazin-1-yl or hexahydro-1H-1,4-diazepin-1-yl which is substituted in the 4-position by methyl or ethyl,   R 6  denotes alkyl with from 1 to 4 carbon atoms,   R 7  denotes alkyl with from 1 to 4 carbon atoms,   A denotes straight-chain or branched alkylene with from 1 to 5 carbon atoms and   m denotes 2 or 3, or an acid-addition salt thereof.     
     
     
       2. A substituted thienobenzodiazepinone according to claim 1 wherein R 3  denotes --N(R 4 )R 5 , or a acid-addition salt thereof. 
     
     
       3. A thienobenzodiazepinone according to claim 1 wherein R 1  denotes --H or alkyl with from 1 to 4 carbon atoms,   R 2  represents halo or has one of the meanings of R 1 ,   R 3  denotes --N(R 4 )R 5 ,   R 4  denotes alkyl with from 1 to 4 carbon atoms or alkenyl with from 3 to 5 carbon atoms,   R 5  has one of the meanings of R 4  or represents --(CH 2 ) m  --N(R 6 )R 7 , or N(R 4 )R 5  denotes morpholino, pyrrolidino, piperidino, hexahydroazepin-1-yl, piperazin-1-yl which is optionally substituted in the 4-position by methyl, ethyl or benzyl, 2,4-dimethylpiperazin-1-yl or hexahydro-1H-1,4-diazepin-1-yl which is substituted in the 4-position by methyl or ethyl,   R 6  denotes alkyl with from 1 to 4 carbon atoms,   R 7  denotes alkyl with from 1 to 4 carbon atoms,   A denotes straight-chain or branched alkylene with from 1 to 5 carbon atoms and   m denotes 2 or 3, or a pharmacologically-acceptable acid-addition salt thereof.     
     
     
       4. A substituted thienobenzodiazepinone according to claim 3 wherein R 1  denotes a hydrogen atom, methyl or ethyl,   R 2  represents chloro or one of the meanings of R 1 ,   R 3  denotes --N(R 4 )R 5 ,   R 4  denotes alkyl with from 1 to 4 carbon atoms or alkenyl with from 3 or 4 carbon atoms,   R 5  has the meaning of R 4  or denotes morpholino, pyrrolidino, piperidino, hexahydroazepin-1-yl, piperazin-1-yl which is substituted in the 4-position by methyl, ethyl or benzyl, 2,4-dimethylpiperazin-1-yl or hexahydro-1H-1,4-diazepin-1-yl which is substituted in the 4-position by methyl or ethyl,   R 6  denotes methyl or ethyl,   R 7  denotes methyl or ethyl,   m denotes 2 or 3 and   A denotes straight-chain or branched alkylene with 1 or 2 carbon atoms, or an acid-addition salt thereof.     
     
     
       5. A compound according to claim 3 in which R 1  denotes --H, methyl or ethyl; R 2  represents chloro or has one of the meanings of R 1  ; R 4  denotes methyl or ethyl, R 5  has the meaning of R 4  or represents --(CH 2 ) m  --N(R 6 )R 7 , or --N(R 4 )R 5  denotes pyrrolidino, piperidino or hexahydroazepin-1-yl; each of R 6  and R 7  denotes methyl or ethyl; m denotes 2; and A denotes methylene; or a pharmacologically-acceptable acid-addition salt thereof. 
     
     
       6. A compound according to claim 3 in which R 1  denotes --H, methyl or ethyl; R 2  represents chloro or has one of the meanings of R 1  ; R 4  and R 5 , together with the nitrogen atom to which both are bound, denote piperazin-1-yl which is substituted in the 4-position by methyl or ethyl; and A denotes methylene; or a pharmacologically-acceptable acid-addition salt thereof. 
     
     
       7. A compound according to claim 3 in which R 1  denotes --H or methyl; R 2  denotes --H or methyl; R 4  and R 5 , together with the nitrogen atom to which both are bound, denote piperazin-1-yl which is substituted in the 4-position by methyl; and A denotes methylene; or a pharmacologically-acceptable acid-addition salt thereof. 
     
     
       8. A compound according to claim 3 which is 9,10-dihydro-4-[(4-methylpiperazin-1-yl)acetyl]-4H-thieno[3,4-b][1,5]benzodiazepin-10-one or a pharmacologically-acceptable acid-addition salt thereof. 
     
     
       9. A compound according to claim 3 which is 9,10-dihydro-3-methyl-4[(4-methylpiperazin-1-yl)acetyl]-4H-thieno[3,4-b][1,5]benzodiazepin-10-one or a pharmacologically-acceptable acid-addition salt thereof. 
     
     
       10. A medicament composition in which a pharmaceutical excipient is combined with a compound according to claim 3, the amount of the latter being from 0.5 to 95 percent by weight of the composition. 
     
     
       11. A medicament composition having a pharmaceutical excipient and a sufficient amount, per unit dose, of a compound according to claim 3 to prevent or reduce the effects of stomach or intestinal disorders. 
     
     
       12. A medicament composition having, per unit dose, a pharmaceutical excipient and from 0.1 to 500 mg of a compound according to claim 3. 
     
     
       13. A method for the prophylaxis or treatment of a stomach or intestinal disorder of the type of acute and chronic ulcus ventriculi and ulcus duodeni, gastritis and hyperacid gastric irritation which comprises administering to a mammal subject to or afflicted with such a disorder an effective amount of a compound according to claim 7. 
     
     
       14. A method for the prophylaxis or treatment of acute and chronic ulcus ventriculi and ulcus duodeni, gastritis and hyperacid gastric irritation which comprises administering to a mammal subject to or afflicted with such a disorder an effective amount of a compound according to claim 3.